The Essential Role of 17-Octadecynoic Acid in the Pathogenesis of Periapical Abscesses

J Endod. 2023 Feb;49(2):169-177.e3. doi: 10.1016/j.joen.2022.12.002. Epub 2022 Dec 14.

Abstract

Introduction: Periapical abscesses are 1 of the most frequent pathologic lesions in the alveolar bone. Recently, we have identified 17-octadecynoic acid (17-ODYA) as the highest unique metabolite in periapical abscesses. Therefore, the aim of this study was to investigate the immunologic and pathophysiological roles of this metabolite in the initiation and development of periapical abscesses.

Methods: Periodontal ligament fibroblasts and peripheral blood mononuclear cells were treated with 17-ODYA. Gene expression analysis and interleukin (IL)-8 release were determined using quantitative real-time polymerase chain reaction and enzyme-linked immunosorbent assay. Macrophage polarization and cytokine release were also determined using flow cytometry and Luminex bioassay (R&D Systems, Minneapolis, MN), respectively.

Results: In periodontal ligament fibroblasts, 17-ODYA caused significant (P < .0001) up-regulation of IL-1α, IL-1β, IL-6, matrix metalloproteinase-1, and monocyte chemoattractant protein-1 at 10 μmol/L after 6 days of treatment and up-regulation of platelet-derived growth factor alpha and vascular endothelial growth factor alpha at all tested concentrations after 2 days of treatment. In peripheral blood mononuclear cells, 17-ODYA significantly increased the expression of IL-1α, IL-1β, IL-6, matrix metalloproteinase-1, and monocyte chemoattractant protein-1 at 10 μmol/L (P < .0001) and vascular endothelial growth factor alpha and platelet-derived growth factor alpha at 1 μmol/L 17-ODYA (P < .0001). 17-ODYA polarized macrophages toward a proinflammatory phenotype (M1) and suppressed the release of pro- and anti-inflammatory cytokines. 17-ODYA significantly enhanced the release of IL-8.

Conclusions: This study was the first to identify the pathologic role of 17-ODYA in the development of periapical abscesses. The results of this study are important in shedding light on the pathogenesis of periapical abscesses in relation to microbial metabolites.

Keywords: 17-octadecynoic acid; acute inflammation; immune response; interleukin-8; metabolite.

MeSH terms

  • Chemokine CCL2*
  • Humans
  • Interleukin-6
  • Leukocytes, Mononuclear
  • Matrix Metalloproteinase 1
  • Periapical Abscess*
  • Platelet-Derived Growth Factor
  • Tumor Necrosis Factor-alpha / metabolism
  • Vascular Endothelial Growth Factor A

Substances

  • Chemokine CCL2
  • 17-octadecynoic acid
  • Matrix Metalloproteinase 1
  • Interleukin-6
  • Vascular Endothelial Growth Factor A
  • Platelet-Derived Growth Factor
  • Tumor Necrosis Factor-alpha